The Effects Of Apolipoprotein E Genetic Polymorphism On The Repair Of Tight Junctions Of Blood Brain Barrier Following Traumatic Brain Injury

Objective: To explore the effects and underlying mechanism ofapolipoprotein E（APOE）genetic polymorphism on the repair of bloodbrain barrier(BBB) after traumatic brain inury(TBI).Methods: Human APOE knock-in(KI) mice (ε3, ε4), APOEknockout(KO) mice and APOE wild-type(WT) mice were randomlydivided into TBI group, sham-operation group and control group, andcontrol cortical injury was produced by PSI TBI-Device. Blood-brainbarrier permeability to large and small molecules were evaluated bymeasuring Evans Blue(EB,961kDa) and Sodium Fluorescein(NaFI,376kDa) extravasation into the cerebral parenchyma at1,3and7day post-TBI.waters content in brain was determined using dry and wet weights.Western blot and qRT-PCR were performed to determine the expressionand transcription of tight junction associated protein claudin-5and occludinat7day post-TBI.Results: The BBB permeabilities both to EB and NaFI in ε4and KO control mice were significantly higher than those in ε3and WT controlmice. After TBI the significant increases in BBB permeabilities either toEB or to NaFI occurred in every genotype mice compared with the controland sham-operation groups. There were no differences in EB permeabilityand NaFI permeability among the four genotype groups at1,3d after TBI.But at7d post-inury the differences in recovery of were observed. At7dpost-inury, the permeability to EB in ε3or WT groups returned to levels ofits control respectively (P>0.05) while the permeability to EB in ε4and KOgroups stayed higher than that of the control groups respectively(P<0.01),and the permeability to NaFI in all the groups were maintained higher thanthose in respective control groups, with significantly higher extravasationof NaFI in ε4and KO groups compared with ε3and WT groups(P<0.01).There was no statistical differences in waters content of brain among thefour groups at1,3and7day after TBI. The transriptions and expressions ofoccludin and claudin-5in ε4and KO mice at7day post brain injury weresignificantly lower than those in ε3and WT mice.Conclusion: APOE Plays a important role in maintainance andrestoration of BBB function and ε4may weaker the function of BBB andimpede recovery of BBB after TBI through its cffect on tight junction.